A second “door” for coronavirus was found in human cells

Chinese scientists have discovered another target for the SARS-CoV-2 coronavirus on the surface of human cells. This is the CD147 protein, which, incidentally, is used not only by the previous coronavirus, the causative agent of SARS, but also by malarial plasmodium. By blocking this protein, the researchers managed to stop the spread of the virus in cell culture. Clinical trials of the corresponding blocking drug have already begun. The work was published on the bioRxiv preprint portal.

The medicine for SARS-CoV-2 coronavirus can be sought in various ways: for example, try to prevent it from multiplying inside the cells or stimulate its own cell defense systems. But there is another way – to block the virus from entering the cells.

The attack of the virus on the target begins with the fact that it adheres with its surface proteins to the proteins on the cell membrane. Then the virus membrane fuses with the cell, and the internal content of the viral particle (RNA gene) is inside the cell. Until now, SARS-CoV-2, like its predecessor, SARS-CoV, the causative agent of SARS, has been thought to bind best with the cellular protein ACE2. However, the new coronavirus has four surface proteins, so it is logical to assume that it will have several targets, that is, binding points to the cell.

Ke Wang, along with colleagues at Fourth Military Medical University in Xi’an, described yet another such “door” inside a cage that SARS-CoV-2 can use. Back in 2005, after an outbreak of SARS, they noticed that SARS-CoV could bind to the CD147 receptor on the surface of cells. This is a protein from the immunoglobulin family. Apparently, it has several functions: for example, it starts the work of metalloproteinases – proteins, which reconstructs the extracellular substance in tissues. Since the previous target, ACE2, was found to be common in two viruses, they suggested that the new coronavirus would also bind to CD147.

To test this, the researchers infected a cell culture of the human kidney with coronavirus. Then they treated it with anti-CD147 antibodies and measured the number of damaged cells, as well as the concentration of viral genomes in the culture medium. It turned out that with an antibody concentration of 3 μg / ml, it was possible to achieve almost one hundred percent stopping the spread of the virus between cells.

Then, the authors showed by immunofluorescence analysis that the surface protein of coronavirus SP and CD147 are able to interact with each other. And finally, the cells infected with the coronavirus were stained with antibodies to these proteins. Inside the cells, SP and CD147 were near, which confirms the assumption that CD147 can help the virus penetrate into the cells.

On the left is a kidney cell infected with a coronavirus. A black arrow indicates a viral particle inside the cell. On the right is the colocalization of the viral protein SP (red arrow) and CD147 (yellow arrow). Wang et al. / bioRxiv, 2020

CD147 is a target not only for coronaviruses, but also for malaria – it is precisely this molecule on the surface of red blood cells that the malaria plasmodium “grabs”. Therefore, the CD147 antibody-blocker has long existed in the form of several drugs. In parallel with the publication of scientific data, Chinese scientists began a clinical trial of these drugs to combat SARS-CoV-2. They believe that closing this “door” is more logical than the previous one. Blockade of ACE2 is fraught with various side effects, including for the lungs, which already suffer most during infection. At the same time, the blockade of CD147, in their opinion, should not cause such consequences.